A 50% Reduction of Excitability but Not of Intercellular Coupling Affects Conduction Velocity Restitution and Activation Delay in the Mouse Heart

Computer simulations suggest that intercellular coupling is more robust than membrane excitability with regard to changes in and safety of conduction. Clinical studies indicate that SCN5A (excitability) and/or Connexin43 (Cx43, intercellular coupling) expression in heart disease is reduced by approximately 50%. In this retrospective study we assessed the effect of reduced membrane excitability or intercellular coupling on conduction in mouse models of reduced excitability or intercellular coupling. Epicardial activation mapping of LV and RV was performed on Langendorff-perfused mouse hearts having the following: 1) Reduced excitability: Scn5a haploinsufficient mice; and 2) reduced intercellular coupling: Cx43(CreER(T)/fl) mice, uninduced (50% Cx43) or induced (10% Cx43) with Tamoxifen. Wild type (WT) littermates were used as control. Conduction velocity (CV) restitution and activation delay were determined longitudinal and transversal to fiber direction during S(1)S(1) pacing and S(1)S(2) premature stimulation until the effective refractory period. In both animal models, CV restitution and activation delay in LV were not changed compared to WT. In contrast, CV restitution decreased and activation delay increased in RV during conduction longitudinal but not transverse to fiber direction in Scn5a heterozygous animals compared to WT. In contrast, a 50% reduction of intercellular coupling did not affect either CV restitution or activation delay. A decrease of 90% Cx43, however, resulted in decreased CV restitution and increased activation delay in RV, but not LV. Reducing excitability but not intercellular coupling by 50% affects CV restitution and activation delay in RV, indicating a higher safety factor for intercellular coupling than excitability in R

Twelve-lead electrocardiogram: The advantages of an orderly frontal lead display including lead -aVR

Background: It is possible that efforts in ECG review by both young experienced clinicians are currently discouraged-and risk to be completely dismissed-by the conventional (ie, disorderly) display of the frontal plane leads, with lead aVR at -150degrees. Methods: We reviewed studies on the usefulness of leads aVR and -aVR as well as on the history of the frontal leads in electrocardiography. Results: Lead aVR and particularly, lead -aVR, provide useful information when systematically analyzed. in addition, if lead -aVR is examined in its anatomically logical sequence, ie, aVL, 1, -aVR, 11, aVF, and 111, the frontal plane of the 12-lead ECG is more easily understood. This "panoramic" or "orderly" display is in common use in countries such as Sweden, but it is rarely seen in the United States. Conclusions: ECG interpretation would be enhanced by displaying the limb leads in an orderly arrangement that starts with lead aVL and ends with lead 111, and many ECG changes would be ideally displayed by a lead -aVR at 30degrees